Arrowhead Pharmaceuticals is looking to file a new drug application (NDA) with the US Food and Drug Administration (FDA) after announcing full data from a pivotal trial of its lead candidate, plozasiran.
The Phase III Palisade study (NCT05089084) met its primary endpoint of fasting triglyceride level and all multiplicity-controlled key secondary endpoints, including statistically significant reductions in triglycerides (TGs), apolipoprotein C-III (APOC3), and the incidence of acute pancreatitis (AP).
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The trial is investigating plozasiran in patients with familial chylomicronemia syndrome (FCS), a severe and rare genetic disease with no approved treatment in the US. The trial enrolled patients with persistent chylomicronemia, with or without a genetic diagnosis.
Arrowhead’s chief medical scientist Dr Bruce Given said: “Based on the data generated to date, we view plozasiran as potentially best-in-class and supportive of development across the spectrum of triglyceride disorders.
“We showed that in PALISADE a high proportion of patients receiving plozasiran achieved triglyceride levels below guideline-directed risk thresholds associated with the risk of acute pancreatitis, which is a critical treatment goal that physicians communicate to us frequently.”
Patients in the trial were randomly assigned to receive 25mg or 50mg plozasiran or placebo every three months. After ten months, the median reduction from baseline in the fasting triglyceride level was -80% in the 25mg plozasiran group, -78% in the 50mg plozasiran group, and -17% in the placebo group.
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By GlobalDataThere were also notable reductions in the median triglyceride level after as early as one month of treatment. After 10 months, APOC3 was significantly reduced with median reductions of -93% in the 25mg plozasiran group, -96% in the 50mg plozasiran group, and -1% in the placebo group.
In the final alpha-controlled secondary efficacy endpoint, patients receiving plozasiran achieved an 83% reduction in the risk of developing acute pancreatitis versus placebo. A total of two cases occurred in two of 50 patients (4%) receiving plozasiran, and seven cases occurred in five of 25 patients (20%) receiving placebo.
Plozasiran remained safe and tolerable with the most common adverse events (AE) being abdominal pain, Covid-19, nasopharyngitis, headache, nausea, back pain, upper respiratory tract infection, and diarrhoea. Severe adverse events were more common in the placebo group.
Arrowhead presented the data during a presentation at the European Society of Cardiology (ESC) Congress 2024 in London, UK.
Based on these positive findings, Arrowhead intends to file the NDA by year-end 2024 and plans to seek regulatory approval with additional global regulatory authorities thereafter.
Plozasiran is a small interfering RNA (siRNA) that acts by targeting APOC3. By silencing the ApoC3 gene, the drug reduces elevated triglyceride levels.
The biotech announced the full trial data three months after it shelved the cardiovascular disease asset, zodasiran, so it could funnel more resources into plozasiran.
Earlier this year, Arrowhead announced it would be making its way into the obesity space with two gene therapies.
